Vascular disruption has been heavily implicated in COVID-19 pathogenesis and may predispose the neurological sequelae associated with the condition now known as long COVID. To date, no studies have objectively assessed blood-brain barrier (BBB) function in individuals with neurological complications stemming from prior SARS-CoV-2 infection. Here, we explored the neurobiological effects of SARS-CoV-2 infection in humans with acute infection (n = 76) and those with persistent long COVID with and without neurological impairment. Following acute infection, patients with neurological impairment had increased serum S100β, indicative of BBB disruption. Furthermore, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in long COVID patients (n = 32), we observed elevated BBB permeability in distinct neuroanatomical regions including the frontal cortex, occipital lobe and temporal lobes which correlated with global brain volume and white matter volume deficits in patients with neurological impairment. Patients with neurological impairment had increased levels of blood-based biomarkers including GFAP, TGFβ and IL8 with levels of TGFβ that correlated with BBB permeability and structural brain changes. Peripheral blood mononuclear cells isolated from unaffected and long COVID patients had persistent upregulation of inflammatory markers including IFNA/G and showed increased adhesion to human brain endothelial cells in vitro. Finally, exposure of endothelial cells to serum from long COVID patients induced increases in ICAM-1, VCAM-1 and TNF irrespective of neurological sequelae. Together, these data suggest that sustained systemic inflammation and persistent localised BBB dysfunction is a feature of long COVID-associated neurological impairment. Importantly, this may also be therapeutically relevant in the treatment and clinical management of this patient group.

Vascular disruption has been heavily implicated in COVID-19 pathogenesis and may predispose the neurological sequelae associated with the condition now known as long COVID. To date, no studies have objectively assessed blood-brain barrier (BBB) function in individuals with neurological complications stemming from prior SARS-CoV-2 infection. Here, we explored the neurobiological effects of SARS-CoV-2 infection in humans with acute infection (n = 76) and those with persistent long COVID with and without neurological impairment. Following acute infection, patients with neurological impairment had increased serum S100β, indicative of BBB disruption. Furthermore, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in long COVID patients (n = 32), we observed elevated BBB permeability in distinct neuroanatomical regions including the frontal cortex, occipital lobe and temporal lobes which correlated with global brain volume and white matter volume deficits in patients with neurological impairment. Patients with neurological impairment had increased levels of blood-based biomarkers including GFAP, TGFβ and IL8 with levels of TGFβ that correlated with BBB permeability and structural brain changes. Peripheral blood mononuclear cells isolated from unaffected and long COVID patients had persistent upregulation of inflammatory markers including IFNA/G and showed increased adhesion to human brain endothelial cells in vitro. Finally, exposure of endothelial cells to serum from long COVID patients induced increases in ICAM-1, VCAM-1 and TNF irrespective of neurological sequelae. Together, these data suggest that sustained systemic inflammation and persistent localised BBB dysfunction is a feature of long COVID-associated neurological impairment. Importantly, this may also be therapeutically relevant in the treatment and clinical management of this patient group.

Background: The incidence of anaphylaxis appears to be increasing worldwide with cases in the community outnumbering those in the hospital setting. General practice (GP) surgeries and pharmacies, based in the community, are often the first point of contact for many patients suffering from anaphylaxis.Objectives: To determine if studied GP surgeries and pharmacies have an anaphylaxis protocol on site and have access to an anaphylaxis kit; to explore GP’s and pharmacists’ personal experiences with management of anaphylaxis.Methods: A cross-sectional, questionnaire-based study was performed examining anaphylaxis protocols in a sample of general practices and pharmacies from some counties in Ireland. This consisted of a sample from rural and urban settings. The study commenced in October 2014.Results: Nineteen of 24 GPs (79%) and 9 (29%) pharmacies had an anaphylaxis protocol (P < 0.001). Twenty-four (100%) GP practices and 12 pharmacies (39%) surveyed had an anaphylaxis kit on site. Twelve GPs (50%) had treated a patient with anaphylaxis in the surgery while 8 (33%) had treated a patient in the community. One pharmacist (3%) had witnessed anaphylaxis in practice. Two pharmacies and one GP had been contacted by local businesses to alert them to a case of anaphylaxis.Conclusion: In contrast to national and international guidelines only 79% of GPs and 29% of pharmacies in this study from Ireland had an anaphylaxis protocol onsite.

Background Background: We describe the clinical and neuropathological features of a patient with T-cellmediated paraneoplastic limbic encephalitis, parkinsonism, hypothermia, and narcolepsy-like presentation associated with endometrial carcinoma. Objectives Objectives: This patient with prominent parkinsonism and narcolepsy broadens the phenotype of known paraneoplastic syndromes and demonstrates the importance of investigation for occult malignancy even in the absence of paraneoplastic antibodies. Methods Methods: This is a case report with diagnosis confirmed at postmortem. ResultsResults: Paraneoplastic antibodies were not detected. The initial improvement with immunosuppression was short lived, and postmortem neuropathological examination demonstrated encephalitis with predominant T-cell infiltration affecting the hypothalamus and extending to the brainstem, suggestive of a paraneoplastic syndrome. ConclusionsConclusions: Although the possibility of a novel antibody cannot be ruled out, consideration must also be given to recent demonstration of purely T-cell-mediated neuronal destruction in the context of paraneoplastic syndromes.

Autosomal dominant optic atrophy plus syndrome is a rare cause of blindness and sensorineural deafness, usually presenting with insidious onset in childhood. Other clinical manifestations are variable but include, peripheral neuropathy, myopathy, opthalmoplegia, ataxia and spastic paraparesis.We present a 50-year-old gentleman brought to clinic with a history of a slowly progressive gait difficulty. He was blind and deaf since childhood but no diagnosis had been made. He had no relevant family history. Examination revealed bilateral optic atrophy on fundoscopy. He was unable to stand unassisted and had reduced reflexes in the lower limbs. MRI brain and spine, together with routine bloods including neuropathy screen were unremarkable. Nerve conduction studies/EMG showed evidence of a large fibre sensorimotor axonal peripheral neuropathy, which was worse in the lower limbs. Given his constel- lation of symptoms, genetic testing was arranged and revealed a heterozygous pathogenic variant in OPA1 gene. This was consistent with a diagnosis of autosomal dominant optic atrophy plus syndrome.This condition is rare and often first detected in childhood. Diagnosis can be challenging due to variable clinical phenotypes and markedly variable expression of disease within families. There is a need for strong clinical suspicion for the disease in any patient with a history of blindness.declanbrennan.1@ucdconnect.ie56